Eugene Goldwasser, PhD, 1922-2010, biochemist behind blockbuster drug

December 20, 2010

Eugene Goldwasser, PhD, the Alice Hogge and Arthur A. Baer professor emeritus of biochemistry and molecular biology at the University of Chicago and the scientist who first purified erythropoietin--the hormone that stimulates the production of red blood cells--died from complications related to advanced prostate cancer on Friday, Dec. 17, 2010, at his home in the Hyde Park neighborhood of Chicago. He was 88.

Generally regarded as the "father of EPO," a drug that helped launch the biotechnology revolution, Goldwasser led the team that succeeded, after 25 years of concentrated effort, in purifying first sheep, then human erythropoietin, a discovery that has enabled millions of dialysis patients and anemic patients with other diseases to live longer and more productive lives.

He was not so successful in a far less intense effort to persuade the University to patent his discovery--a novel concept at the time.

Instead, he worked as a consultant for the start-up biotechnology company, Amgen, sharing his expertise, methods, and some of his purified erythropoietin to help them discover and clone the erythropoietin gene. Amgen did patent the production of recombinant erythropoietin in 1987 and secured FDA approval of the drug in 1989 for treatment of anemia in patients undergoing dialysis. Although patent squabbles persisted for two more decades, the market for erythropoietin quickly blossomed to several billion dollars a year.

"Gene Goldwasser was such a nice, quiet, unassuming guy, you would never know that he had done something so absolutely monumental," said colleague Donald Steiner, MD, the A.N. Pritzker distinguished service professor of biochemistry and molecular biology at the University of Chicago. "His work with erythropoietin has had enormous impact. It is one of the great contributions to science or medicine of the 20th Century, comparable to the discovery of insulin."

"He was someone who took enormous delight in doing science," said Gary Toback, MD, PhD, professor of medicine at the University of Chicago. "He was also a valued mentor, colleague and friend."

A prolific researcher and author, Goldwasser published more than 150 research studies and 60 book chapters--almost all of them about some aspect of erythropoietin, also known as "epo." He authored two short books: a biography of his mentor, Leon Jacobson, MD, and a recently completed history of the quest for erythropoietin, which should come out in 2011.

It was a request from Jacobson, who ran University's Argonne Cancer Research Hospital after World War II, that triggered Goldwasser's interest in this hormone, which he initially considered "just a laboratory curiosity." Jacobson wanted to understand how the blood-forming process recovered after radiation exposure. So in 1955 he asked Goldwasser to isolate and purify the biochemical signal that regulated the growth of new red blood cells.

"I thought it would be a short diversion for about six months and then I'd get back to other research," Goldwasser recalled.

In 1957, by removing various organs from rats and looking for the onset of anemia, he had traced production of the signal to the kidneys, which explained why patients with chronic kidney disease were often anemic and suggested that erythropoietin could be found in urine.

By 1971 his lab had purified 6 millionths of an ounce of the hormone from 125 gallons of plasma from anemic sheep. Erythropoietin, he noted in a press statement at the time, "is present, even in enriched sources, in an extremely minute amount."

The breakthrough came in 1973, when Takaji Miyake, MD, a Japanese physician who cared for patients suffering from aplastic anemia, contacted Goldwasser. They agreed to collaborate. While Goldwasser procured funding, Miyake collected 2,550 liters of urine from his patients. On Christmas Day, 1975, he arrived in Chicago with his concentrated samples. Within 18 months they had eight precious milligrams of the potent human hormone. "We put it in rats," recalled Goldwasser, "and it worked like a charm."

Most of the existing supply went to a small, unpublished clinical trial, development of an assay to measure hormone levels in the blood, and early attempts to determine the amino-acid composition, a first step toward cloning the gene. In 1977, at the urging of colleagues and the federal agencies that funded his lab--the Department of Energy and the National Institutes of Health--Goldwasser filled out the patent disclosure form and submitted it to the University.

"After submitting the form, I promptly forgot about it," he wrote years later, "since nothing was ever done about filing for a patent. I believe the rules at the time would have allowed me to file a patent for myself if the agency or the University decided not to--another point to perhaps be rueful about."

Filing for patents "was not generally done at the time," noted Toback.

"Biogen asked Gene to join their board of epo advisors," recalled Chicago colleague, Robert Haselkorn, PhD, professor of biochemistry and molecular genetics. "Gene looked at the list of others on the board and decided that they were mediocre. Then, Amgen went through the same exercise and asked Gene to be their sole advisor on epo. He accepted, declining the board role but signing on as a consultant." In 1985, a team from Amgen cloned the gene using two probes derived by amino acid sequence analysis of Gene's purified human erythropoietin samples. "The rest is history."

By 1986, industrial production was underway. The first reports from clinical studies appeared in late 1986 and 1987, confirming that the drug could correct anemia in patients with kidney failure. By 1996, annual sales in the United States exceeded $1 billion. Amgen subsequently funded a professorship in Goldwasser's department.

"The enormous success of epo still astonishes me," Goldwasser wrote in a 1996 biographical essay. "It is still gratifying to me to see how effective epo is in correcting the anemia of dialysis patients, and how it spares them repeated transfusions."

Less gratifying was the subsequent recognition, in the late 1990s, that athletes had been injecting the drug to boost their red blood cell counts for a competitive advantage. In 1998, one-third of the 21 teams in the Tour de France were expelled or withdrew in an epo-based doping scandal, a development that deeply dismayed Goldwasser.

The benefits of his discovery however, far outweighed its potential for abuse. "Recombinant human erythropoietin is arguably the most successful therapeutic application of recombinant DNA technology to date," said a 2009 editorial in the New England Journal of Medicine. "Since the initial reports … documented a cure of the anemia of chronic kidney disease with recombinant human erythropoietin, well over a million patients have been treated with it effectively and with minimal drug-related toxicity."

Born Oct. 14, 1922, in Brooklyn, New York, Eugene Goldwasser spent his first decade there before the Depression forced his father to close their small clothing manufacturing business and move to Kansas City, where his brother ran a similar business. In high school, Goldwasser developed an interest in science. He won a scholarship to the University of Chicago, where he majored in biological sciences and, after the Japanese attack on Pearl Harbor, worked as a research assistant in the University's Toxicity Laboratory, a federally funded program to assess chemical and biological risks. He completed his bachelor's degree in biochemistry in March, 1943.

In 1944, he was drafted into the United States Army. He served for two years as a biochemist at Fort Detrick, Maryland, working on anthrax. In 1946, he returned to Chicago as a graduate student. He married Florence Cohen of Chicago in 1949 and completed his PhD in biochemistry in 1950. He spent the next two years in a post-doctoral fellowship studying nucleic acids (part of it alongside fellow postdoc James Watson, a future Nobel laureate) with Herman Kalckar at the Institute for Cytophysiology in Copenhagen, Denmark.

In 1952, Goldwasser returned to Chicago as an instructor in biochemistry. He stayed for the rest of his career, rising to professor of biochemistry and molecular biology in 1963 and chair of the department from 1984 to 1985. He retired at age 65 in 1987, but remained active in his laboratory and served again as department chair from 1994 to 1998. He also served as chair of the Committee on Developmental Biology from 1976 to 1991. Goldwasser retired again in 2002.

He received several honors, including election as a Fellow of the American Academy of Arts & Sciences and, most recently, the 2005 Prince Mahidol Award, from Thailand, given for "outstanding performance and/or research in the field of medicine for the benefit of mankind."

His first wife died in 1981. In 1986, he married Deone Jackman, a Hyde Park neighbor, who was introduced to him by a mutual friend. He is survived by Jackman; three sons: Thomas, of San Francisco; Matthew, of Chicago; and James, of New York; two step children, Tom and Tara Jackman; and seven grandchildren.

His friends and children recall him as an avid and gifted photographer, sailor, traveler, and, in his younger years, skier. "He loved art, music, and the Blackhawks, recalled James Goldwasser. He particularly liked reading, added Toback, "which may explain why two of his three sons are in the book business."

A memorial service will be held at Rockefeller Memorial Chapel on Monday, Jan. 24 at 4 p.m.